A Multicentre Study on 50 Cases with Thrombotic Thrombocytopenic Purpura in the Czech Republic: Recurrent Mutation in ADAMTS13 Gene as a Cause of a Hereditary Thrombotic Thrombocytopenic Purpura

Abstract number: P1505

Hrachovinová¹ I, Salaj¹ P, Rittich¹ [Scaron], Suttnar¹ J, Dyr¹ JE, Jinoch¹ P, [Scaron]uláková² T, Pták² J, Ďulí[ccaron]ek³ P, Seeman⁴ T

¹¹Institute of Hematology and Blood Transfusion, Praha, Czech Republic ¹¹Institute of Hematology and Blood Transfusion, Praha, Czech Republic ²²FNsP Ostrava, Czech Republic ³³FN Hradec Králové, Czech Republic ⁴⁴FN Motol Praha, Czech Republic

Thrombotic thrombocytopenic purpura is characterized by thrombocytopenia, microangiopathic hemolysis, neurological abnormality, and renal dysfunction. Similar manifestations also occur in patients with the hemolytic uremic syndrome or other disorders. Recent studies demonstrate that severe deficiency of the von Willebrand factor cleaving metalloprotease, ADAMTS13, causes TTP. Aim of our prospective study in the years 2002–2004 was to characterize patients sent to our lab with a clinical diagnosis of TTP. Samples were taken immediately prior to the first plasma exchange therapy or in a remission of the recurrent form of disease. We measured activity of ADAMTS13 (VWF-CP) with modified method of the Furlan et al., 1996. Mutation screening was carried out by sequencing of the ADAMTS13 gene in nine patients with diagnosis of familiar form and four patients with an acquired form of TTP. Nearly two third of patients (29/50) got a severe vWF-CP deficiency with activity than 6% of normal. Antibodies against VWF-CP were found in the 16 of them (55%). Ten patients with severe ADAMTS13 deficiency revealed a hereditary form of TTP. Thirteen of 50 patients had borderline severe or moderate deficiency. After a follow-up was complete, most of these patients had an alternative diagnosis (e.g. sepsis, cancer). Eight of 50 patients (16%) displayed VWF-CP values >50%. This group manifested a severe renal failure in seven of eight patients. It was significantly higher than in the severe ADAMTS13 deficiency group. Mutation analysis of the ADAMTS13 gene in patients with familiar form of TTP brought interesting results. We found a mutation 4143insA in 6 of 7 unrelated individuals. This investigation represents an advantage in the differential diagnosis of TTP. Such high incidence in small territory about 3 mill people suspects the founder effect of this mutation.